posted on 2021-06-07, 21:43authored byMaría Negrete, Elena Romero-Ben, Alicia Gutiérrez-Valencia, Cristian Rosales-Barrios, Eva Alés, Teresa Mena-Barragán, Juan A. Flores, M Castillejos, Patricia de la Cruz-Ojeda, Elena Navarro-Villarán, Carmen Cepeda-Franco, Noureddine Khiar, Jordi Muntané
Hepatocellular
carcinoma (HCC) is the sixth most common neoplasia
and the fourth most common cause of cancer-related mortality worldwide.
Sorafenib is the first-line molecular therapy for patients in an advanced
stage of HCC. However, the recommended clinical dose of Sorafenib
is associated with several complications, which derive from its lack
of cell specificity and its very low water solubility. To circumvent
these drawbacks, in the present study we developed two sugar-coated
polydiacetylene-based nanomicelles-Sorafenib carriers targeting mannose
and asialoglycoprotein receptors (MR and ASGPR, respectively). The
strategies allowed the inducement of apoptosis and reduction of cell
proliferation at a nanomolar, instead of micromolar, range in liver
cancer cells. The study showed that, contrary to literature data,
Sorafenib included into the pMicMan (Man = mannose) vector (targeting
MR) is more efficient than pMicGal (Gal = galactose) (targeting ASGPR).
Indeed, pMicMan increased the endosomal incorporation with an increased
intracellular Sorafenib concentration that induced apoptosis and reduced
cell proliferation at a low concentration range (10–20 nM).